Endostatin gene therapy inhibits intratumoral macrophage M2 polarization

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dc.contributor.author Foguer, Karen [UNIFESP]
dc.contributor.author Braga, Marina de Souza [UNIFESP]
dc.contributor.author Schatzmann Peron, Jean Pierre
dc.contributor.author Bortoluci, Karina Ramalho [UNIFESP]
dc.contributor.author Bellini, Maria Helena [UNIFESP]
dc.date.accessioned 2020-07-22T13:23:17Z
dc.date.available 2020-07-22T13:23:17Z
dc.date.issued 2016
dc.identifier http://dx.doi.org/10.1016/j.biopha.2016.01.035
dc.identifier.citation Biomedicine & Pharmacotherapy. Paris, v. 79, p. 102-111, 2016.
dc.identifier.issn 0753-3322
dc.identifier.uri https://repositorio.unifesp.br/handle/11600/56147
dc.description.abstract Background: Renal cell carcinoma (RCC) is a highly vascularized cancer resistant to chemotherapy and radiotherapy. RCC is frequently infiltrated with immune cells, with macrophages being the most abundant cell type. Alternatively activated M2 macrophages are known to contribute to tumor progression. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we investigated the impact of ES gene therapy on the polarization of tumor-associated macrophages (TAMs) in lung metastases from tumor-bearing mice. Methods: BALB/c mice divided into three groups: Normal, Control and ES-treated. Tumor-bearing mice were treated with ES-transduced cells or control cells over ten days. At the end of the study, plasma was collected, and pulmonary macrophages were isolated and used for FACS or RT-PCR. ELISA tests were used to analyze plasma and cell culture supernatant cytokines. Results: ES treatment significantly reduced the levels of anti-inflammatory and pro-angiogenic cytokines, including IL4, IL-10, IL-13 and VEGF. Gene expression of M2 markers, such as IL-10, Arg-1, VEGF and YM-1, declined significantly. Flow cytometry showed a reduction in the number of M2 F4/80 + CD36 + CD206 + CD209+ macrophages and in IL-10 secretion by these cells. Reduced levels of IL-10 were also found in the culture supernatants of the ES-treated group. Conclusions: Our research corroborates previous observations that ES has an important anti-tumoral role. However, aside from promoting interferon-g secretion and an effective T cell response, we show here that this switch is extended to TAMs, complicating the maintenance of pro-tumorigenic M2 macrophages and thus favoring tumor elimination. (C) 2016 Elsevier Masson SAS. All rights reserved. en
dc.description.sponsorship FAPESP
dc.description.sponsorship CNPq
dc.description.sponsorship CAPES/PNPD
dc.format.extent 102-111
dc.language.iso eng
dc.publisher Elsevier France-Editions Scientifiques Medicales Elsevier
dc.relation.ispartof Biomedicine & Pharmacotherapy
dc.rights Acesso aberto
dc.subject Renal cell carcinoma en
dc.subject Endostatin en
dc.subject Tumor-associated macrophages en
dc.title Endostatin gene therapy inhibits intratumoral macrophage M2 polarization en
dc.type Artigo
dc.description.affiliation Univ Fed Sao Paulo, Div Nephrol, Sao Paulo, Brazil
dc.description.affiliation IPEN CNEN, Dept Biotechnol, Sao Paulo, Brazil
dc.description.affiliation Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Dept Biol Biol Sci, Sao Paulo, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Div Nephrol, Sao Paulo, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Dept Biol Biol Sci, Sao Paulo, Brazil
dc.description.sponsorshipID FAPESP: 2011/18703-2
dc.description.sponsorshipID CNPq: 473102/2012-9
dc.identifier.file WOS000373527100014.pdf
dc.identifier.doi 10.1016/j.biopha.2016.01.035
dc.description.source Web of Science
dc.identifier.wos WOS:000373527100014
dc.coverage Paris
dc.citation.volume 79



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